Making the right cut in the right location

β-Amyloid Processing In Alzheimer's disease, pathogenic β-amyloid (Aβ) accumulates in the brain. Two enzymes, γ- and β-secretase, produce Aβ by cleaving amyloid precursor protein. Therapeutically, the β-secretase cleavage reaction would be a good one to target, but inhibiting the enzyme also inhibits the cleavage of other key substrates, and so it can be harmful. Ben Halima et al. exploited the fact that Aβ cleavage occurs within an endocytic compartment, whereas γ- and β-secretase cleave other important substrates at the cell surface. They targeted a β-secretase inhibitor to endosomes and successfully inhibited Aβ production in a variety of different cells. These encouraging findings may help in the search for an Alzheimer's disease therapy with minimal off-target side effects. Cell Rep. 10.1016/j.celrep.2016.01.076 (2016).